Highly active antiretroviral therapy (HAART) can effectively control the amount of viruses in patients to an undetectable extent, but it is hard to be remove precursor viruses of latently infected HIV-1 (human immunodeficiency virus type 1) after integrated into a genome of a host to form a reservoir pool. Long-term medication is necessary for patients to suppress a viral replication, and a rebound of the viral replication may be caused once withdrawal of drugs. How to clear latent infection of HIV-1 has become a bottleneck problem for completely curing AIDS.
Cytokines such as interleukin-2 (IL-2) and anti-CD3 etc. have been used for activating latent infection of HIV-1, which activate the cells in an overall level, leading to huge poisonous side effects on an organism. A plurality of histone deacetylase inhibitors (HDACi) are also latent activators studied more currently. On one hand, abnormal expressions of other genes are easily caused due to activation of HDACi to genes being broad-spectrum effects; on the other hand, HDACi having better effects in vitro such as valproc acid (VPA) and Vorinostat (ie. Suberoylanilide hydroxamic acid, SAHA), and being not good in clinical manifestations, cannot be put into practical use. Therefore, finding out new, strong in specificity, highly effective and safe latent activators is an urgent mission.
HIV-1 Tat is a specific trans-activation factor of HIV-1, which specifically binds to TAR of HIV-1 5′ LTR, raising several hundreds of times the transcription of HIV-1 mRNA. TAT protein is also a critical factor in the latent infection of HIV-1. This protein with cell-penetrating peptides has been proven to have a function of efficiently penetrating cytomembrane; and has been designed as a vaccine for HIV-1 used in clinical experiment, which is relatively safe for human body. However, Tat protein has been proven to have a function of inducing apoptosis, and may affect functions of immunocyte.